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ABC-04 a Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer (ABC-04)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01242605
Recruitment Status : Completed
First Posted : November 17, 2010
Last Update Posted : May 13, 2016
Information provided by (Responsible Party):
University College, London

Brief Summary:
The objective of this study is to establish the recommended dose of selumetinib, a novel MEK inhibitor for use in combination with gemcitabine and cisplatin.

Condition or disease Intervention/treatment Phase
Biliary Tract Neoplasms Cholangiocarcinoma Gallbladder Neoplasms Drug: selumetinib Drug: gemcitabine Drug: cisplatin Phase 1

Detailed Description:

This trial aims to evaluate the safety and tolerability of selumetinib in combination with CisGem and to establish the recommended dose to take into phase II studies. Pharmacokinetic and pharmacodynamic endpoints will be assessed and preliminary efficacy data will also be collected.

Patients with Advanced Biliary tract Cancer will receive CisGem regimen and selumetinib. A dose de-escalation scheme will be employed to determine the recommended phase II dose of selumetinib.

Patients will be recruited in cohorts of three and assessed for dose limiting toxicity (DLT) during the first cycle of treatment. Depending on the number of DLTs observed, the cohort may be expanded, the next cohort may be enrolled at a lower dose or the dose may be declared the recommended dose. Patients will receive up to eight cycles of CisGem and may continue to receive selumetinib until progression of disease.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ABC-04 a Phase 1B Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer
Study Start Date : February 2012
Actual Primary Completion Date : March 2013
Actual Study Completion Date : May 2016

Arm Intervention/treatment
Experimental: single armed
This is not a randomised trial, there is only one study group. All patients will receive cisplatin/gemcitabine chemotherapy in addition to oral daily dosing of selumetinib
Drug: selumetinib
The starting dose of selumetinib will depend on the cohort. The first dose of selumetinib to be studied will be 75 mg twice daily (bd). Selumetinib will be taken every day (continuously) either once or twice a day, depending on the dose. Treatment with selumetinib may continue until disease progression.
Other Name: AZD6244

Drug: gemcitabine
gemcitabine: taken in combination with cisplatin will be given at 1000 mg/m*2 in 250 - 500 ml 0.9% saline over 30 minutes by intravenous infusion on days 1, and 8 of each 21-day cycle for eight cycles in total

Drug: cisplatin
cisplatin: 25 mg/m*2 in 1000 ml 0.9% saline given over 1 hour followed by 500mls 0.9% saline over 30 minutes followed by gemcitabine on days 1, and 8 of each 21-day cycle for eight cycles in total

Primary Outcome Measures :
  1. To investigate the safety and tolerability of the combination of cisplatin, gemcitabine and selumetinib, and to establish the recommended phase II dose of selumetinib when given in this combination. [ Time Frame: from baseline to 28 days post last patient last treatment ]

    To investigate the safety and tolerability of the combination of cisplatin, gemcitabine (CisGem) and selumetinib and to establish the recommended phase II dose of selumetinib when given in this combination.

    The recommended dose of selumetinib to use in combination with CisGem in future studies will be the dose at which less than 33% of patients experience a DLT. The recommended dose will not be higher than 75mg/m*2

Secondary Outcome Measures :
  1. Response rate [ Time Frame: From baseline to end of treatment ]
    To make a preliminary assessment of efficacy in terms of tumour control.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • A histopathological or cytological diagnosis of non-resectable, recurrent or metastatic biliary tract (intra- or extra-hepatic), gallbladder or ampullary carcinoma
  • ECOG performance status 0, 1, or 2
  • Age ≥ 18
  • Estimated life expectancy > 3 months
  • Adequate haematological function:

    • Haemoglobin 9g/dL (prior transfusions for patients with low haemoglobin are allowed)
    • WBC >/= 3.0 x 10*9/L
    • Absolute neutrophil count (ANC) >/= 1.5 x 10*9/L
    • Platelet count >/= 100 x 10*9/L
  • Adequate liver function:

    • Total bilirubin ≤1.5 x upper limit of normal (ULN) OR ≤ 3.0 x upper limit of normal (ULN) if stable for a duration of two weeks
    • ALT and/or AST & alkaline phosphatase ≤ 5 x ULN
  • Adequate renal function:

    • Serum urea and serum creatinine < 1.5 times ULN
    • Calculated GFR >/= 45 mL/min. If the calculated GFR is below 45ml/min, isotope EDTA confirmation of adequate renal function is required
  • Capable of giving written informed consent
  • Prior therapy is allowed (provided there has been a full recovery):

    • Surgery (non-curative operation), must have evidence on nonresectable disaes progression prior to trial entry
    • Radiotherapy, must have clear evidence of disease progression prior to inclusion
    • Prior adjuvant chemotherapy is allowed provided neither gemcitabine nor cisplation were used and treatment was completed 28 days prior to trial entry.

Exclusion Criteria:

  • Any prior exposure to MEK, Ras, or Raf inhibitors
  • Cardiac conditions as follows:

    • Uncontrolled hypertension (BP ≥150/95 despite optimal therapy)
    • Heart failure (NYHA Class II or above)
    • Prior or current cardiomyopathy
    • Baseline LVEF ≤50%
    • Atrial fibrillation with heart rate >100 bpm
    • Unstable ischaemic heart disease (MI within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly).
  • Incomplete recovery from previous surgery.
  • Patients undergoing current treatment with curative intent.
  • History of prior malignancy that could interfere with the response evaluation (exceptions include in-situ carcinoma of the cervix treated by cone-biopsy/resection, non-metastatic basal and/or squamous cell carcinomas of the skin, any early stage (stage I) malignancy adequately resected for cure greater than 5 years previously).
  • Any evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial.
  • Any psychiatric or other disorder (e.g brain metastases) likely to impact on informed consent.
  • Pregnancy or breast-feeding. Women of child-bearing potential should must have a negative pregnancy test prior to study entry AND be using an adequate contraception method, which must be continued for 3 months after completion of chemotherapy
  • NB. Whilst not excluded, patients with significant impaired hearing must be made aware of potential ototoxicity and may choose not to be included. If included, baseline audiograms are recommended and should be followed by repeat audiograms prior to cycle 2.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01242605

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United Kingdom
Hammersmith Hospital
London, United Kingdom
University College London Hospital
London, United Kingdom
The Christie Hospital
Manchester, United Kingdom
Sponsors and Collaborators
University College, London
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Principal Investigator: John Bridgewater, MBBS UCL

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University College, London Identifier: NCT01242605    
Other Study ID Numbers: UCL/10/0254
2010-018522-39 ( EudraCT Number )
First Posted: November 17, 2010    Key Record Dates
Last Update Posted: May 13, 2016
Last Verified: October 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by University College, London:
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Gallbladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs